Objective To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in hypocaleaemia and parathyroid hormone receptor 1 ( PTHR1 ) of rats with acute necrotizing pancreatitis (ANP).Methods Seventy-two male health adult Spragne-Dawley rats were randomized into three groups:ANP group,ANP treated with SB203580 group (SB group),sham operation group (SO group).Every group was sub-divided into 3,6,12 h group with 8 rats in each one.ANP model was induced by retrograde infusion with 5% sodium taurocholate solution into the biliopancreatie duct.In the SB group,rats were treated with the specific p38MAPK inhibitor:SB203580 30 minutes before the induction of ANP model.The serum level of calcium was determined,the change of phosphorylated p38MAPK and TNFalpha were measured by western blot and the expression of PTHR1 mRNA was determined by quantitative real time RT-PCR.Results 6 h after ANP model induction,the serum levels of calcium in ANP,SB and SO group were (2.50±0.08 ) mmol/L,(2.11±0.06 ) mmol/L and (2.35±0.10 ) mmol/L,respectively;the expression levels of pbosphorylated p38MAPK in bone tissue were 0.14±0.04,0.80±0.06 and 0.33±0.05,respectively;the expression levels of p38MAPK TNF-alpha were 0,0.91±0.04 and 0.44±0.03,respectively;the expression levels of PTHR1 mRNA were 1.00±0.12,0.23±0.04 and 0.44±0.06,respectively.The expression levels of p38MAPK and TNF-α in SB group were significantly lower than those in the ANP group (P ＜ 0.01 );while the expression levels of PTHR1 mRNA and calcium were significantly higher than those in the ANP group (P ＜0.01 ).Conclusions P38MAPK signal transduction pathway may mediate the development of hypocaleaemia in the course of ANP,and hypoealcaemia could be improved by blocking this pathway.